CD28 and neoplasm: Alternatively, the function of IR can be neutralized, for example by engineered PD-1 “dominant negative” receptors (DNR) lacking signaling motifs, or even reversed by chimeric PD1/CD28, CTLA-4/CD28, TIGIT/CD28 and CD200/CD28 “switch” receptors that fuse IR exodomains with costimulatory endodomains to increase cytokine secretion and anti-tumor activity [118,119,120,121,122,123].